Lupus-like autoimmunity caused by defects in T-cell signal transduction.

Systemic lupus erythematosus (SLE) is a prevalent, non-organ-specific autoimmune disease that is partially caused by genetic factors. Types of genetic factors that can contribute to lupus have been revealed by studies of naturally occurring and genetically engineered mutant mice which are susceptible to this disease. Notably, a number of mutant mice have been reported that point to defective T-lymphocyte signal transduction as one potential cause of lupus. Deficient expression of adapter proteins, cell cycle control proteins, ubiquitin ligases and transcription factors, and impaired phosphatidylinositol 3-kinase (PI3-kinase) and Ras signaling in T-cells, all promote lupus in mice. These findings have important implications for the causes and treatment of human SLE.